Download Angina pectoris

Angina pectoris
• Sudden, severe, pressing chest pain and radiating to the neck,
jaw, back, and arms. The episodes are transient, stay between
15 sec to 15 min.
• Caused by a reduction in the coronary blood flow to a level
that does not meet the requirements of the myocardium,
leading to what is called ischemia.
• This oxygen supply imbalance may caused by:
a. a spasm of the vascular smooth muscles
b. obstruction of blood vessels caused by
atherosclerosis.
Types of angina
• Angina has three overlapping patterns, which are caused by
varying combination of increased myocardial demand and
decreased myocardial perfusion.
A. Stable angina, the most common form, and characterized by a
burning heavy or squeezing feeling in the chest.
Caused by reduction of coronary perfusion due to coronary
atherosclerosis. So the heart become susceptible to ischemia
whenever there is demand, such as exercise, emotional
excitement.
This type is rapidly relieved by rest or nitroglycerin.
Types of angina
B. Unstable angina, lies between stable angina and
infarction, Often unrelated to exercise.
myocardial
The symptoms are not relieved by rest or nitroglycerin.
unstable angina require more aggressive therapy, for example
treatments of dyslipidemias, hypertension, anti-platelets.
C. Variant angina, occurs at rest and caused by coronary artery
spasm (i.e. caused by contraction of the smooth muscle tissue
in the vessel walls rather than directly by atherosclerosis)
Generally, this type rapidly responds to nitroglycerin and
calcium channel blockers.
Organic nitrates
• These compounds cause a rapid reduction in the myocardial
oxygen demand, and so provide a rapid relief for the angina
symptoms.
• They are effective in the three types of angina pectoris.
• Their mechanism of action summarized in a decrease
coronary spasm or vasoconstruction and in an increase
perfusion of the myocardial by relaxing the coronary arteries.
• Members of this group include: isosorbide dinitrate,
isosorbide mononitrate, and Nitroglycerine.
2.Pharmacological mechanism
Organic nitrates
NO
guanylyl cyclase
cGMP
cGMP dependent protein kinase
intracellular Ca2+
vascular smooth muscle relaxation
Organic nitrates
• All of the three agents are effective but they differ in the
onset and duration of action.
• For rapid relief of an ongoing attack that precipitate by
exercise and emotional stress, sublingual nitroglycerine is the
drug of choice.
• At therapeutics dose nitroglycerine has two major effects:
a. dilation of the large veins, resulting in pooling of blood in
the veins (diminish preload and reduce the work of heart).
orthostatic hypotension and syncope.
b. dilates the coronary arteries.
Beneficial and Deleterious Effects of Nitrates in the Treatment of Angina
Result
1. Potential beneficial effects
Decreased ventricular volume
Decreased arterial pressure
Decreased ejection time
Decreased myocardial oxygen
requirement
Vasodilation of epicardial coronary arteries
Relief of coronary artery spasm
Increased collateral flow
Improved perfusion to ischemic
myocardium
Improved subendocardial
perfusion
Decreased left ventricular diastolic pressure
2. Potential deleterious effects
Reflex tachycardia
Reflex increase in contractility
Decreased diastolic perfusion time due to
tachycardia
Increased myocardial oxygen
requirement
Decreased coronary perfusion
Organic nitrates
• The time to onset the action varies from 1 min for
nitroglycerine to 1 hr for isosorbide mononitrate .
• Significant first pass metabolism of nitroglycerine occurs so it
administrated sublingually or transdermally (patch).
• Isosorbide mononitrate has long duration of action due to its
ability to avoid first pass effect (so it is administrated orally).
Organic nitrates
• Adverse effect:
a. headache (throbbing headach) is a common early side
effect of nitrates, which is usually decrease after the first few
days (patient develop tolerance).
Contraindicated in if intracranial pressure elevated.
b. high doses can cause postural hypotension syncope, also can
result in tachycardia.
• Sildinafil (Viagra) potentiates the action of nitrates, and to
avoid the dangerous hypotension, an interval of six hour
between the two agents is recommended.
Tolerance
• Tolerance to the action of the nitrates develops rapidly, the
blood vessels become desensitized to the vasodilation.
• Why????? diminished release of nitric oxide resulting from
depletion of tissue thiol compounds may be partly
responsible for tolerance to nitroglycerin.
• The tolerance can be overcame by providing a daily “nitrate
free intervals” to restore sensitivity to the drug (this interval
are usually 10 – 12 hr at night)
Important notes to your patient
• The conventional sublingual tablet form of
nitroglycerin may lose potency when stored as
a result of volatilization and adsorption to
plastic surfaces. Therefore, it should be kept in
tightly closed glass containers. Nitroglycerin is
not sensitive to light.
• spray is equally effective; it has a shelf life of
two to three years and does not require
refrigeration
General Guidline
• One or fewer — People who have one or fewer angina episodes per
week are usually advised to take sublingual (under the tongue)
nitroglycerin when an episode of angina occurs and immediately
before activities that could cause angina.
• Two or more — People who have two or more angina episodes per
week are usually advised to take longer-acting antianginal medicines.
This may include a long-acting nitrate or a beta blocker.
• Treatment with added medicines — If angina persists while taking
one medicine, a second medicine may be added. Combined
treatment may relieve angina more effectively than a single
medicine.
-adrenergic blocking agents
• They suppress the heart by blocking 1 receptors, and so
reduce the work of the heart by decreasing the cardiac output
and blood pressure.
• They reduce the frequency and the severity of angina attack.
• The cardioselective 1 agents, such as acebutolol and
atenolol and metoprolol are preferred.
• They combined with nitrates to increase exercise duration and
tolerance.
Beta-Blockers
• Decrease myocardial oxygen consumption
• Blunt exercise response
• Try to avoid drugs
sympathomimetic activity
with
intrinsic
• First line therapy in all patients with stable
angina
Undesirable effects
• An increase in end-diastolic volume and an
increase in ejection time, both of which tend
to increase myocardial oxygen requirement.
• These deleterious effects of beta -blocking
agents can be balanced by the concomitant
use of nitrates.
-adrenergic blocking agents
2.cilinical uses
stable and unstable angina
myocardia infarction
3.contraindication
variant angina,
bronchial asthma,
bradycardia,
Calcium channel blockers
•
Inhibiting the entrance of calcium into cardiac and smooth
muscles cells of the coronary arteries and so they lower blood
pressure.
A.
Nifidipine, arterioles vasodilation effect with minimal effect
on the heart, and is useful in the treatments of angina caused
by spontaneous coronary spasm (Variant angina).
B.
Verapamil, slow cardiac conduction directly, and thus
decrease oxygen demand, so should be avoided with patient
with a congestive heart failure due to its negative inotropic
effect on the heart.
C.
Diltiazem has similar effect on the heart to Verapamil.
Calcium Channel Blockers
Mechanisms of Action
•
•
•
•
•
•
Arterial dilation/after-load reduction
Coronary arterial vasodilation
Prevention of coronary vasoconstriction
Enhancement of coronary collateral flow
Improved subendocardial perfusion
Slowing of heart rate with diltiazem, verapamil
Calcium channel blockers
• Long-acting CCB's (e.g. amlodipine) or sustained release
formulations of short-acting CCB's (e.g. nifedipine, felodipine,
verapamil and diltiazem) are preferred,
to minimize fluctuations of plasma concentrations and
cardiovascular effects.
• Side-effects are also concentration-dependent, and mainly
related to the arterial vasodilator responses
(headache, flushing and ankle oedema);
these effects are more pronounced with dihydropyridine
CCB's.
Verapamil and Diltiazem
• In patients with relatively low blood pressure, dihydropyridines
can cause further deleterious lowering of pressure.
Verapamil and diltiazem appear to produce less
hypotension and may be better tolerated in these
circumstances.
• In patients with a history of atrial tachycardia, flutter,
and fibrillation, verapamil and diltiazem provide a
distinct advantage because of their antiarrhythmic
effects.
Comparison
• Meta-analyses comparing effects of beta-blockers and CCB's
in stable angina pectoris indicate that:
beta-blockers are more effective than CCB's in reducing anginal
episodes,
but that effects on exercise tolerance and ischemia of the two
drug classes are similar
• However, CCB's are especially effective in patients with
vasospastic (Prinzmetal) angina
Combination Therapy of Angina
• Use of more than one class of antianginal agent can reduce
specific undesirable effects of single agent therapy
Beta-Blockers or
Nitrates Plus
Channel Blockers
Beta-Blockers or
Alone
Channel Blockers
Effect
Nitrates Alone
Heart Rate
Reflex Increase
Decrease*
Decrease
Afterload
Decrease
Decrease
Decrease
Preload
Decrease
Increase
Contractility
Reflex increase
Decrease*
None
Ejection time
Decrease
Increase
None
Undesireable effects are shown in italics
None or decrease
Recommendations for pharmacological therapy of
vasospastic angina
• Treatment with calcium antagonists and if
necessary nitrates in patients whose coronary
arteriogram is normal or shows only nonobstructive lesions.
• Decrease vasospasm of coronary vessels
(calcium channel blockers are efficacious in
>70% of patients; increase oxygen delivery)